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The Reactome Knowledgebase (https://reactome.org), an Elixir and GCBR core biological data resource, provides manually curated molecular details of a broad range of normal and disease-related biological processes. Processes are annotated as an ordered network of molecular transformations in a single consistent data model. Reactome thus functions both as a digital archive of manually curated human biological processes and as a tool for discovering functional relationships in data such as gene expression profiles or somatic mutation catalogs from tumor cells. Here we review progress towards annotation of the entire human proteome, targeted annotation of disease-causing genetic variants of proteins and of small-molecule drugs in a pathway context, and towards supporting explicit annotation of cell- and tissue-specific pathways. Finally, we briefly discuss issues involved in making Reactome more fully interoperable with other related resources such as the Gene Ontology and maintaining the resulting community resource network., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: Data are needed to assess the capacity of HIV care facilities to implement recommended Ending the HIV Epidemic activities., Setting: US HIV care facilities., Methods: We analyzed 2021 survey data from 514 facilities that were recruited from a census of facilities providing care to a national probability sample of US adults with HIV. We present weighted estimates of facility characteristics, services, and policies and estimates of the proportion of all US HIV patients attending these facilities., Results: Among HIV care facilities, 37% were private practices, 72% were in areas with population >1 million, and 21% had more than 1000 HIV patients. Most provided preexposure prophylaxis (83%) and postexposure prophylaxis (84%). More than 67% of facilities provided HIV-specific stigma or discrimination training for all staff (covering 70% of patients) and 66% provided training on cultural competency (covering 74% of patients). A majority of patients attended facilities that provided on-site access to HIV/sexually transmitted infection (STI) transmission risk reduction counseling (89%); fewer had on-site access to treatment for substance use disorders (35%). We found low provision of on-site assistance with food banks or meal delivery (14%) and housing (33%). Approximately 71% of facilities reported using data to systematically monitor patient retention in care. On-site access to adherence tools was available at 58% of facilities; 29% reported notifying patients of missed prescription pickups., Conclusion: Results indicate some strengths that support Ending the HIV Epidemic-recommended strategies among HIV care facilities, such as high availability of preexposure prophylaxis/postexposure prophylaxis, as well as areas for improvement, such as provision of staff antistigma trainings and adherence supports., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Guidelines and implementation of tuberculosis preventive treatment (TPT) vary by age and HIV status. Specifically, TPT is strongly recommended for people living with HIV/AIDS (PLWHA) and household contacts younger than 5 years but only conditionally recommended for older contacts. Cost remains a major barrier to implementation. The aim of this study was to evaluate the cost-effectiveness of TPT for household contacts and PLWHA., Methods: We developed a state-transition model to simulate short-course TPT for household contacts and PLWHA in 29 high-incidence countries based on data from previous studies and public databases. Our primary outcome was the incremental cost-effectiveness ratio, expressed as incremental discounted costs (2020 US$, including contact investigation costs) per incremental discounted disability-adjusted life year (DALY) averted, compared with a scenario without any TPT or contact investigation. We propagated uncertainty in all model parameters using probabilistic sensitivity analysis and also evaluated the sensitivity of results to the screening algorithm used to rule out active disease, the choice of TPT regimen, the modelling time horizon, assumptions about TPT coverage, antiretroviral therapy discontinuation, and secondary transmission., Findings: Between 2023 and 2035, scaling up TPT prevented 0·9 (95% uncertainty interval 0·4-1·6) people from developing tuberculosis and 0·13 (0·05-0·27) tuberculosis deaths per 100 PLWHA, at an incremental cost of $15 (9-21) per PLWHA. For household contacts, TPT (with contact investigation) averted 1·1 (0·5-2·0) cases and 0·7 (0·4-1·0) deaths per 100 contacts, at a cost of $21 (17-25) per contact. Cost-effectiveness was most favourable for household contacts younger than 5 years ($22 per DALY averted) and contacts aged 5-14 years ($104 per DALY averted) but also fell within conservative cost-effectiveness thresholds in many countries for PLWHA ($722 per DALY averted) and adult contacts ($309 per DALY averted). Costs per DALY averted tended to be lower when compared with a scenario with contact investigation but no TPT. The cost-effectiveness of TPT was not substantially altered in sensitivity analyses, except that TPT was more favourable in analysis that considered a longer time horizon or included secondary transmission benefits., Interpretation: In many high-incidence countries, short-course TPT is likely to be cost-effective for PLWHA and household contacts of all ages, regardless of whether contact investigation is already in place. Failing to implement tuberculosis contact investigation and TPT will incur a large burden of avertable illness and mortality in the next decade., Funding: Unitaid., Competing Interests: Declaration of interests REC reports funding from Unitaid through a grant subcontract to Johns Hopkins (2017-20-IMPAACT4TB). All other authors declare no competing interests., (Copyright © 2023 World Health Organization (acting as the host organization for Unitaid). Published by Elsevier Ltd. All rights reserved. This is an Open Access article published under the CC BY 3.0 IGO license which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that Unitaid or WHO endorses any specific organisation, products or services. The use of the Unitaid or WHO logo is not permitted. This notice should be preserved along with the article's original URL.)

Background: Attention-deficit/hyperactivity disorder (ADHD) and associated behavioral disorders are highly prevalent in children and adolescents, yet many of them do not receive the care they need. Digital mental health interventions (DMHIs) may address this need by providing accessible and high-quality care. Given the necessity for high levels of caregiver and primary care practitioner involvement in addressing ADHD symptoms and behavioral problems, collaborative care interventions that adopt a whole-family approach may be particularly well suited to reduce symptoms of inattention, hyperactivity, and opposition in children and adolescents., Objective: The purpose of this study is to use member (ie, child and adolescent) data from Bend Health, Inc, a collaborative care DMHI that uses a whole-family approach to address child and adolescent mental health concerns, to (1) determine the effects of a collaborative care DMHI on inattention, hyperactivity, and oppositional symptoms in children and adolescents and (2) assess whether the effects of a collaborative care DMHI vary across ADHD subtypes and demographic factors., Methods: Caregivers of children and adolescents with elevated symptoms of inattention, hyperactivity, or opposition assessed their children's symptom severity approximately every 30 days while participating in Bend Health, Inc. Data from 107 children and adolescents aged 6-17 years who exhibited clinically elevated symptoms at baseline were used to assess symptom severity across monthly assessments (inattention symptom group: n=91, 85.0%; hyperactivity symptom group: n=48, 44.9%; oppositional symptom group: n=70, 65.4%). The majority of the sample exhibited elevated symptoms of at least 2 symptom types at baseline (n=67, 62.6%)., Results: Members received care for up to 5.52 months and attended between 0 and 10 coaching, therapy, or psychiatry sessions through Bend Health, Inc. For those with at least 2 assessments, 71.0% (n=22) showed improvements in inattention symptoms, 60.0% (n=9) showed improvements in hyperactivity symptoms, and 60.0% (n=12) showed improvements in oppositional symptoms. When considering group-level change over time, symptom severity decreased over the course of treatment with Bend Health, Inc, for inattention (average decrease=3.51 points, P=.001) and hyperactivity (average decrease=3.07 points, P=.049) but not for oppositional symptoms (average decrease=0.70 points, P=.26). There was a main effect of the duration of care on symptom severity (P<.001) such that each additional month of care was associated with lower symptom scores., Conclusions: This study offers promising early evidence that collaborative care DHMIs may facilitate improvements in ADHD symptoms among children and adolescents, addressing the growing need for accessible and high-quality care for behavioral health problems in the United States. However, additional follow-up studies bolstered by larger samples and control groups are necessary to further establish the robustness of these findings., (©Darian Lawrence-Sidebottom, Landry Goodgame Huffman, Jennifer Huberty, Clare Beatty, Monika Roots, Kurt Roots, Amit Parikh, Rachael Guerra, Jaclyn Weiser. Originally published in JMIR Formative Research (https://formative.jmir.org), 26.04.2023.)

Background: A growing body of evidence supports the efficacy of measurement-based care (MBC) for children and adolescents experiencing mental health concerns, particularly anxiety and depression. In recent years, MBC has increasingly transitioned to web-based spaces in the form of digital mental health interventions (DMHIs), which render high-quality mental health care more accessible nationwide. Although extant research is promising, the emergence of MBC DMHIs means that much is unknown regarding their effectiveness as a treatment for anxiety and depression, particularly among children and adolescents., Objective: This study uses preliminary data from children and adolescents participating in an MBC DMHI administered by Bend Health Inc, a mental health care provider that uses a collaborative care model to assess changes in anxiety and depressive symptoms during participation in the MBC DMHI., Methods: Caregivers of children and adolescents participating in Bend Health Inc for anxiety or depressive symptoms reported measures of their children's symptoms every 30 days throughout the duration of participation in Bend Health Inc. Data from 114 children (age 6-12 years) and adolescents (age 13-17 years) were used for the analyses (anxiety symptom group: n=98, depressive symptom group: n=61)., Results: Among children and adolescents participating in care with Bend Health Inc, 73% (72/98) exhibited improvements in anxiety symptoms and 73% (44/61) exhibited improvement in depressive symptoms, as indicated by either a decrease in symptom severity or screening out of completing the complete assessment. Among those with complete assessment data, group-level anxiety symptom T-scores exhibited a moderate decrease of 4.69 points (P=.002) from the first to the last assessment. However, members' depressive symptom T-scores remained largely stable throughout their involvement., Conclusions: As increasing numbers of young people and families seek DMHIs over traditional mental health treatments due to their accessibility and affordability, this study offers promising early evidence that youth anxiety symptoms decrease during involvement in an MBC DMHI such as Bend Health Inc. However, further analyses with enhanced longitudinal symptom measures are necessary to determine whether depressive symptoms show similar improvements among those involved in Bend Health Inc., (©Landry Goodgame Huffman, Darian Lawrence-Sidebottom, Jennifer Huberty, Monika Roots, Kurt Roots, Amit Parikh, Rachael Guerra, Jaclyn Weiser. Originally published in JMIR Pediatrics and Parenting (https://pediatrics.jmir.org), 20.04.2023.)

Pathway databases provide descriptions of the roles of proteins, nucleic acids, lipids, carbohydrates, and other molecular entities within their biological cellular contexts. Pathway-centric views of these roles may allow for the discovery of unexpected functional relationships in data such as gene expression profiles and somatic mutation catalogues from tumor cells. For this reason, there is a high demand for high-quality pathway databases and their associated tools. The Reactome project (a collaboration between the Ontario Institute for Cancer Research, New York University Langone Health, the European Bioinformatics Institute, and Oregon Health & Science University) is one such pathway database. Reactome collects detailed information on biological pathways and processes in humans from the primary literature. Reactome content is manually curated, expert-authored, and peer-reviewed and spans the gamut from simple intermediate metabolism to signaling pathways and complex cellular events. This information is supplemented with likely orthologous molecular reactions in mouse, rat, zebrafish, worm, and other model organisms. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Browsing a Reactome pathway Basic Protocol 2: Exploring Reactome annotations of disease and drugs Basic Protocol 3: Finding the pathways involving a gene or protein Alternate Protocol 1: Finding the pathways involving a gene or protein using UniProtKB (SwissProt), Ensembl, or Entrez gene identifier Alternate Protocol 2: Using advanced search Basic Protocol 4: Using the Reactome pathway analysis tool to identify statistically overrepresented pathways Basic Protocol 5: Using the Reactome pathway analysis tool to overlay expression data onto Reactome pathway diagrams Basic Protocol 6: Comparing inferred model organism and human pathways using the Species Comparison tool Basic Protocol 7: Comparing tissue-specific expression using the Tissue Distribution tool., (© 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.)

Hepatitis A virus can cause severe and prolonged illness in persons with HIV (PWH). In July 2020, the Advisory Committee on Immunization Practices (ACIP) expanded its recommendation for hepatitis A vaccination to include all PWH aged ≥1 year. We used a decision analytic model to estimate the value of vaccinating a cohort of adult PWH aged ≥20 years with diagnosed HIV in the United States using a limited societal perspective. The model compared 3 scenarios over an analytic horizon of 1 year: no vaccination, current vaccine coverage, and full vaccination. We incorporated the direct medical costs and nonmedical costs (i.e., public health costs and productivity loss). We estimated the total number of infections averted, cost to vaccinate, and incremental cost per case averted. Full implementation of the ACIP recommendation resulted in 775 to 812 fewer adult cases of hepatitis A in 1 year compared with the observed vaccination coverage. The incremental cost-effectiveness ratio for the full vaccination scenario was $48,000 for the 2-dose single-antigen hepatitis A vaccine and $130,000 for the 3-dose combination hepatitis A and hepatitis B vaccine per case averted, compared with the observed vaccination scenario. Depending on type of vaccine, full hepatitis A vaccination of PWH could lead to ≥80% reduction in the number of cases and $48,000 to $130,000 in additional cost per case averted. Data on hepatitis A health outcomes and costs specific to PWH are needed to better understand the longer-term costs and benefits of the 2020 ACIP recommendation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Objective: To describe the landscape of needs for housing assistance among people with HIV (PWH) and availability of Housing Opportunities for People with AIDS (HOPWA) funding with respect to housing service needs, nationally and for 17 US jurisdictions., Design: The CDC Medical Monitoring Project (MMP) is an annual, cross-sectional survey designed to report nationally and locally representative estimates of characteristics and outcomes among adults with diagnosed HIV in the United States., Methods: We analyzed 2015-2020 data from MMP and 2019 funding data from HOPWA. Weighted percentages and 95% confidence intervals (CIs) for national and jurisdiction-level estimates were reported., Results: Nationally, 1 in 4 (27.7%) PWH had shelter or housing service needs. Among those who needed housing services, 2 in 5 (40.4%) did not receive them (range: 21.3% in New York to 62.3% in Georgia). Reasons for unmet needs were multifactorial and varied by jurisdiction. Available 2019 HOPWA funding per person in need would cover up to 1.24 months of rent per person nationally (range: 0.53 months in Virginia to 9.54 months in Puerto Rico), and may not have matched housing assistance needs among PWH in certain jurisdictions., Conclusion: Addressing housing service needs necessitates a multipronged approach at the provider, jurisdiction, and national level. Locally, jurisdictions should work with their partners to understand and address housing service needs among PWH. Nationally, distribution of HOPWA funding for housing services should be aligned according to local needs; the funding formula could be modified to improve access to housing services among PWH., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To evaluate HIV care continuum trends over time among women with HIV (WWH)., Design: The Medical Monitoring Project (MMP) is a complex sample survey of adults with diagnosed HIV in the United States., Methods: We used 2015-2019 MMP data collected from 5139 adults with diagnosed HIV infection who identified as cisgender women. We calculated weighted percentages with 95% confidence intervals (CIs) for all characteristics and estimated annual percentage change (EAPC) and the associated 95% CI to assess trends. EAPCs were considered meaningful from a public health perspective if at least 1% with P values less than 0.05., Results: Among cisgender women with diagnosed HIV infection during 2015-2019, 58.8% were Black or African American (95% CI 54.4-63.3), 19% were Hispanic/Latina (95% CI 14.7-23.2), and 16% were Non-Hispanic White (95% CI 14.1-17.9) persons. There was a meaningful increase in the percentage who ever had stage 3 HIV disease from 55.8% (95% CI 51.0-60.5) in 2015 to 61.5% (95% CI 58.1-64.8) in 2019 (EAPC 1.7%; CI 1.5-1.9; P < 0.001). There were no meaningful changes over time among women, overall, in retention in care, antiretroviral therapy (ART) prescription, ART adherence, missed appointments, or recent or sustained viral suppression., Conclusion: The HIV care continuum outcomes among WWH did not meaningfully improve from 2015 to 2019, raising a concern that Ending the HIV Epidemic in the US (EHE) initiative goals will not be met. To improve health and reduce transmission of HIV among WWH, multifaceted interventions to retain women in care, increase ART adherence, and address social determinants of health are urgently needed., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The development of ligands capable of effectively stabilizing highly reactive main-group species has led to the experimental realization of a variety of systems with fascinating properties. In this work, we computationally investigate the electronic, structural, energetic, and bonding features of proximity-enforced group 13-15 homodimers stabilized by a rigid expanded pincer ligand based on the 1,8-naphthyridine (napy) core. We show that the redox-active naphthyridine diimine (NDI) ligand enables a wide variety of structural motifs and element-element interaction modes, the latter ranging from isolated, element-centered lone pairs (e.g., E = Si, Ge) to cases where through-space π bonds (E = Pb), element-element multiple bonds (E = P, As) and biradical ground states (E = N) are observed. Our results hint at the feasibility of NDI-E 2 species as viable synthetic targets, highlighting the versatility and potential applications of napy-based ligands in main-group chemistry., (© 2022 The Authors. Journal of Computational Chemistry published by Wiley Periodicals LLC.)

Background: Data are scarce on assessing the impact of the COVID-19 pandemic on young people. Aim: To examine changes in crisis text patterns in the United States during the pandemic compared to the prepandemic period. Method: Nonintrusive data from a national digital crisis texting platform were analyzed using an interrupted time series design. Poisson regression with repeated-measures examined help-seeking patterns for stress, anxiety, depression, suicidal thoughts, and other mental health concerns in the pandemic (March 13 to July 20, 2020) compared to the prepandemic period (March 13 to July 20, 2019). Results: An abrupt increase in national crisis response texts occurred during the pandemic for stress and anxiety, substance abuse, bereavement, isolation, and abuse compared to the prepandemic period. Similar trends of excess texts for isolation and abuse were reported among children (relative risk [RR] abuse : 1.16, CI: 1.03, 1.31; RR isolation : 1.15, CI: 1.09, 1.21) and adolescents (RR abuse : 1.17, CI: 1.11, 1.24; RR isolation : 1.08, CI: 1.05, 1.11), bereavement among Black (RR: 1.31, CI: 1.12, 1.54) and Hispanic (RR: 1.28, CI: 1.10, 1.49) texters, and isolation and bereavement in female (RR isolation : 1.09, CI: 1.06, 1.11; RR bereavement : 1.21, CI: 1.13, 1.28) or nonconforming youth (RR isolation : 1.19, CI: 1.08, 1.32; RR bereavement : 1.50, CI: 1.08, 2.09) texters. Conversely, the risks of reporting bullying, depression, relationship issues, and suicidal thoughts as reasons for texting were significantly lower during COVID-19. Limitations: Results may underestimate crisis support-seeking in some groups because demographic data were not captured on all texters. Conclusion: Findings illuminated the real-time crisis response of young people across the United States and can inform more responsive interventions to alleviate the mental health consequences brought on by the COVID-19 pandemic.

Increasing HIV testing, preexposure prophylaxis (PrEP), and antiretroviral therapy (ART) are pillars of the federal Ending the HIV Epidemic in the U.S. (EHE) initiative, with a goal of decreasing new HIV infections by 90% by 2030.* In response to the COVID-19 pandemic, a national emergency was declared in the United States on March 13, 2020, resulting in the closure of nonessential businesses and most nonemergency health care venues; stay-at-home orders also limited movement within communities (1). As unemployment increased during the pandemic (2), many persons lost employer-sponsored health insurance (3). HIV testing and PrEP prescriptions declined early in the COVID-19 pandemic (4-6); however, the full impact of the pandemic on use of HIV prevention and care services and HIV outcomes is not known. To assess changes in these measures during 2019-2021, quarterly data from two large U.S. commercial laboratories, the IQVIA Real World Data - Longitudinal Prescription Database (IQVIA), † and the National HIV Surveillance System (NHSS) § were analyzed. During quarter 1 (Q1) ¶ 2020, a total of 2,471,614 HIV tests were performed, 190,955 persons were prescribed PrEP, and 8,438 persons received a diagnosis of HIV infection. Decreases were observed during quarter 2 (Q2), with 1,682,578 HIV tests performed (32% decrease), 179,280 persons prescribed PrEP (6% decrease), and 6,228 persons receiving an HIV diagnosis (26% decrease). Partial rebounds were observed during quarter 3 (Q3), with 2,325,554 HIV tests performed, 184,320 persons prescribed PrEP, and 7,905 persons receiving an HIV diagnosis. The proportion of persons linked to HIV care, the number who were prescribed ART, and proportion with a suppressed viral load test (<200 copies of HIV RNA per mL) among those tested were stable during the study period. During public health emergencies, delivery of HIV services outside of traditional clinical settings or that use nonclinical delivery models are needed to facilitate access to HIV testing, ART, and PrEP, as well as to support adherence to ART and PrEP medications., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Abstract: Unstably housed sexually active people with human immunodeficiency virus experience both a high incidence of sexually transmitted infections (STI) and barriers to annual STI screening recommended by Centers for Disease Control and Prevention guidelines. We used Medical Monitoring Project data to describe STI testing among unstably housed people with human immunodeficiency virus by attendance at Ryan White HIV/AIDS Program-funded facilities., Competing Interests: Conflict of Interest: None declared., (Copyright © 2022 American Sexually Transmitted Diseases Association. All rights reserved.)

A naphthyridine diimine (NDI) supported bis(germylene) NDI-Ge 2 containing two dicoordinate, coplanar Ge(II) atoms has been synthesised. Computational investigations on NDI-Ge 2 indicated the two Ge(II) atoms are nearly independent. The EDA-NOCV analysis of the [NDI-Ge 2 ][Fe 2 (CO) 6 ] complex revealed the six-electron donor behavior of NDI-Ge 2 , the first example for group-14-element-based bidentate ligands.

Childhood maltreatment may alter fear neurocircuitry, which results in pathological anxiety and depression. One alteration of fear-related behaviors that has been observed in several psychiatric populations is an overgeneralization of fear. Thus, we examined the association between childhood maltreatment and fear generalization in a non-clinical sample of young adults. Two hundred and ninety-one participants underwent differential fear conditioning in a fear-potentiated startle paradigm. One visual stimulus (CS+), but not another (CS-), was associated with an aversive airblast to the throat (US) during acquisition. The next day, participants were tested for their fear responses to the CS+, CS-, and several generalization stimuli (GS) without the presence of the US. Participants also completed questionnaires that assessed symptoms of childhood maltreatment, anxiety, depression, and post-traumatic stress disorder (PTSD). Participants reporting high childhood maltreatment ( n = 71; 23 males, 48 females) exhibited significantly greater anxiety, depression, and symptoms of PTSD than participants reporting low childhood maltreatment ( n = 220; 133 males, 87 females). Females reporting high childhood maltreatment demonstrated significantly enhanced fear learning and greater fear generalization, based on their fear-potentiated startle responses. Our findings suggest that childhood maltreatment may sex-dependently influence the development of fear neurocircuitry and result in greater fear generalization in maltreated females.

The reaction of a cyclic alkyl(amino)carbene (CAAC)-stabilized thiazaborolo[5,4-d]thiazaborole (TzbTzb) with strong Brønsted acids, such as HCl, HOTf (Tf=O 2 SCF 3 ) and [H(OEt 2 ) 2 ][BAr F 4 ] (Ar F =3,5-(CF 3 ) 2 C 6 H 3 ), results in the protonation of both TzbTzb nitrogen atoms. In each case X-ray crystallographic data show coordination of the counteranions (Cl - , OTf - , BAr F 4 - ) or solvent molecules (OEt 2 ) to the doubly protonated fused heterocycle via hydrogen-bonding interactions, the strength of which strongly influences the 1 H NMR shift of the NH protons, enabling tuning of both the visible (yellow to red) and fluorescence (green to red) colors of these salts. DFT calculations reveal that the hydrogen bonding of the counteranion or solvent to the protonated nitrogen centers affects the intramolecular TzbTzb-to-CAAC charge transfer character involved in the S 0 →S 1 transition, ultimately enabling fine-tuning of their absorption and emission spectral features., (© 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Monkeypox virus, an orthopoxvirus sharing clinical features with smallpox virus, is endemic in several countries in Central and West Africa. The last reported outbreak in the United States, in 2003, was linked to contact with infected prairie dogs that had been housed or transported with African rodents imported from Ghana (1). Since May 2022, the World Health Organization (WHO) has reported a multinational outbreak of monkeypox centered in Europe and North America, with approximately 25,000 cases reported worldwide; the current outbreak is disproportionately affecting gay, bisexual, and other men who have sex with men (MSM) (2). Monkeypox was declared a public health emergency in the United States on August 4, 2022. † Available summary surveillance data from the European Union, England, and the United States indicate that among MSM patients with monkeypox for whom HIV status is known, 28%-51% have HIV infection (3-10). Treatment of monkeypox with tecovirimat as a first-line agent is available through CDC for compassionate use through an investigational drug protocol. No identified drug interactions would preclude coadministration of tecovirimat with antiretroviral therapy (ART) for HIV infection. Pre- and postexposure prophylaxis can be considered with JYNNEOS vaccine, if indicated. Although data are limited for monkeypox in patients with HIV, prompt diagnosis, treatment, and prevention might reduce the risk for adverse outcomes and limit monkeypox spread. Prevention and treatment considerations will be updated as more information becomes available., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Objective: To investigate unmet needs for HIV ancillary care services by healthcare coverage type and Ryan White HIV/AIDS Program (RWHAP) assistance among adults with HIV., Design: We analyzed data using the 2017-2019 cycles of the CDC Medical Monitoring Project, an annual, cross-sectional study designed to produce nationally representative estimates of characteristics among adults with diagnosed HIV., Methods: Unmet need was defined as needing, but not receiving, one or more HIV ancillary care services. We estimated prevalence ratios (PRs) and 95% confidence intervals (CIs) using predicted marginal means to examine associations between healthcare coverage type and unmet needs for HIV ancillary care services, adjusting for age. Associations were stratified by receipt of RWHAP assistance., Results: Unmet needs for HIV ancillary care services were highest among uninsured persons (58.7%) and lowest among those with private insurance living with at least 400% of the federal poverty level (FPL; 21.7%). Uninsured persons who received RWHAP assistance were less likely than those who did not receive RWHAP assistance to have unmet needs for HIV clinical support services (aPR: 0.21; 95% CI: 0.16-0.28) and other medical services (aPR: 0.75; 95% CI: 0.59-0.96), but not subsistence services (aPR: 0.97; 95% CI: 0.74-1.27). Unmet needs for other medical services and subsistence services did not differ by RWHAP assistance among those with Medicaid, Medicare, or other healthcare coverage., Conclusions: RWHAP helped reduce some needs for uninsured persons. However, with growing socioeconomic inequities following the coronavirus disease 2019 pandemic, expanding access to needed services for all people with HIV could improve key outcomes., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The HIV Medicine Association of the Infectious Disease Society of America publishes Primary Care Guidance for Persons with Human Immunodeficiency Virus. We assessed receipt of recommended baseline tests among newly diagnosed patients initiating HIV care., Methods: The Medical Monitoring Project is a Centers for Disease Control and Prevention survey designed to produce nationally representative estimates of behavioral and clinical characteristics of adults with diagnosed HIV in the United States. We analyzed data for 725 participants in the 2015-2019 data collection cycles who received an HIV diagnosis within the past 2 years and had ≥1 HIV provider visit. We estimated the prevalence of having recommended tests after the first HIV provider visit and between 3 months before and 3/6 months after the first HIV provider visit and estimated prevalence differences of having 4 combinations of tests by sociodemographic and clinical characteristics., Results: Within 6 months of care initiation, HIV monitoring tests were performed for 91.3% (95% CI, 88.7%-93.8%) of patients; coinfection blood tests, 27.5% (95% CI, 22.5%-32.4%); site-based STI tests, 59.7% (95% CI, 55.4%-63.9%); and blood chemistry and hematology tests, 50.8% (95% CI, 45.8%-55.8%). Patients who were younger, gay, or bisexual were more likely to receive site-based STI tests, and patients receiving care at Ryan White HIV/AIDS Program (RWHAP)-funded facilities were more likely than patients at non-RWHAP-funded facilities to receive all test combinations., Conclusions: Receipt of recommended baseline tests among patients initiating HIV care was suboptimal but was more likely among patients at RWHAP-funded facilities. Embedding clinical decision support in HIV provider workflow could increase recommended baseline testing., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Ancillary care services are essential for supporting care engagement and viral suppression among persons with HIV. Estimating unmet needs for ancillary care services may help address care barriers and improve clinical outcomes, but recent, nationally representative estimates are lacking. Using CDC Medical Monitoring Project data from 2015-2018, we report representative estimates of unmet needs for ancillary care services and associations with HIV clinical outcomes among U.S. adults with HIV. Data were collected through interview and medical record abstraction. We described weighted percentages for all characteristics and associations with HIV clinical outcomes using prevalence ratios with predicted marginal means, adjusting for potential confounding. Substantial unmet needs were reported; unmet needs were higher among persons with social determinants of poor health, persons who engaged in drug use or binge drinking, and those who experienced depression or anxiety. Having unmet needs for care was associated with adverseHIV clinical outcomes, with a dose response effect between number of unmet needs and outcomes. Expanding ancillary care access based on a comprehensive care model, strengthening partnerships between providers to connect patients to essential services, and tailoring services based on need may help reduce disparities in unmet needs and improve outcomes.

Background: The proportion of adults age 50 and older experiencing homelessness is growing. People at risk for homelessness may stay with family and friends to prevent homelessness. Moving in with housed family and friends is a strategy used to exit homelessness. Little is known about these stays with family and friends. This study examined the motivations for and challenges of older adults experiencing homelessness staying with or moving in with family or friends., Methods: We purposively sampled 46 participants from the HOPE HOME study, a cohort of 350 community-recruited adults experiencing homelessness age ≥50 in Oakland, CA. Inclusion criteria included having stayed with housed family/friends for ≥1 nights in the prior 6 months. We sampled 19 family/friends who had hosted participants experiencing homelessness. We conducted separate, semi-structured interviews, summarized, memoed and coded data consistent using a grounded theory approach., Results: Older adults experiencing homelessness reported primarily temporary stays. Motivations for stays on the part of participants included a need for environmental, physical, and emotional respite from homelessness. Both individuals experiencing homelessness and hosts cited the mutual benefits of stays. Barriers to stays included feelings of shame, concerns about burdening the hosts, and interpersonal conflicts between older adults experiencing homelessness and host participants., Conclusions: There are potential opportunities and concerns surrounding temporary stays between older adults experiencing homelessness and their family or friends. Policy solutions should support the potential mutual benefits of temporary stays, while addressing interpersonal barriers to strengthen kinship and friendship networks and mediate the negative impacts of homelessness., Competing Interests: Declaration of conflicting interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To evaluate whether reported prevalence of unemployment, subsistence needs, and symptoms of depression and anxiety among adults with diagnosed HIV during the COVID-19 pandemic were higher than expected., Design: The Medical Monitoring Project (MMP) is a complex sample survey of adults with diagnosed HIV in the United States., Methods: We analyzed 2015-2019 MMP data using linear regression models to calculate expected prevalence, along with corresponding prediction intervals (PI), for unemployment, subsistence needs, depression, and anxiety for June-November 2020. We then assessed whether observed estimates fell within the expected prediction interval for each characteristic, overall and among specific groups., Results: Overall, the observed estimate for unemployment was higher than expected (17% vs. 12%) and exceeded the upper limit of the PI. Those living in households with incomes ≥400% of FPL were the only group where the observed prevalence of depression and anxiety during the COVID-19 period was higher than the PIs; in this group, the prevalence of depression was 9% compared with a predicted value of 5% (75% higher) and the prevalence of anxiety was 11% compared with a predicted value 5% (137% higher). We did not see elevated levels of subsistence needs, although needs were higher among Black and Hispanic compared with White persons., Conclusions: Efforts to deliver enhanced employment assistance to persons with HIV and provide screening and access to mental health services among higher income persons may be needed to mitigate the negative effects of the US COVID-19 pandemic., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Reactome is a database of human biological pathways manually curated from the primary literature and peer-reviewed by experts. To evaluate the utility of Reactome pathways for predicting functional consequences of genetic perturbations, we compared predictions of perturbation effects based on Reactome pathways against published empirical observations. Ten cancer-relevant Reactome pathways, representing diverse biological processes such as signal transduction, cell division, DNA repair and transcriptional regulation, were selected for testing. For each pathway, root input nodes and key pathway outputs were defined. We then used pathway-diagram-derived logic graphs to predict, either by inspection by biocurators or using a novel algorithm MP-BioPath, the effects of bidirectional perturbations (upregulation/activation or downregulation/inhibition) of single root inputs on the status of key outputs. These predictions were then compared to published empirical tests. In total, 4968 test cases were analyzed across 10 pathways, of which 847 were supported by published empirical findings. Out of the 847 test cases, curators' predictions agreed with the experimental evidence in 670 and disagreed in 177 cases, resulting in ∼81% overall accuracy. MP-BioPath predictions agreed with experimental evidence for 625 and disagreed for 222 test cases, resulting in ∼75% overall accuracy. The expected accuracy of random guessing was 33%. Per-pathway accuracy did not correlate with the number of pathway edges nor the number of pathway nodes but varied across pathways, ranging from 56% (curator)/44% (MP-BioPath) for 'Mitotic G1 phase and G1/S transition' to 100% (curator)/94% (MP-BioPath) for 'RAF/MAP kinase cascade'. This study highlights the potential of pathway databases such as Reactome in modeling genetic perturbations, promoting standardization of experimental pathway activity readout and supporting hypothesis-driven research by revealing relationships between pathway inputs and outputs that have not yet been directly experimentally tested., Database Url: www.reactome.org., (© The Author(s) 2022. Published by Oxford University Press.)

The Reactome Knowledgebase (https://reactome.org), an Elixir core resource, provides manually curated molecular details across a broad range of physiological and pathological biological processes in humans, including both hereditary and acquired disease processes. The processes are annotated as an ordered network of molecular transformations in a single consistent data model. Reactome thus functions both as a digital archive of manually curated human biological processes and as a tool for discovering functional relationships in data such as gene expression profiles or somatic mutation catalogs from tumor cells. Recent curation work has expanded our annotations of normal and disease-associated signaling processes and of the drugs that target them, in particular infections caused by the SARS-CoV-1 and SARS-CoV-2 coronaviruses and the host response to infection. New tools support better simultaneous analysis of high-throughput data from multiple sources and the placement of understudied ('dark') proteins from analyzed datasets in the context of Reactome's manually curated pathways., (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Purpose: This study characterized the unobserved patterns in crisis response among youth in the U.S. from March to December 2020 and determined the characteristics of vulnerable subgroups who were at increased risk for suicide due to the pandemic., Methods: A latent class analysis of crisis support-seeking from a national text-based crisis platform, (n = 179,497, aged 24 years or younger) for 11 crisis concerns (e.g., depression, anxiety/stress, suicidal thoughts, isolation, abuse, bereavement, relationships) was performed on three study periods: (1) January 2017 to December 2020, (2) prepandemic: 1 January 2017 to 12 March 2020, and (3) pandemic: 13 March to 20 December 2020. Demographic characteristics (age, race/ethnicity, sexual orientation, and gender identity) were used as predictors for class membership using the three-step method., Results: Four latent classes were identified: (1) depression/isolation/self-harm (D/I/S) (18,694 texters, 10.4%), (2) interpersonal stress/mood-anxiety (I/M) (32,640 texters, 18.2%), (3) suicidal thoughts/depressed (S/D) (34,067, 19.0%), and (4) adjustment/stress (A/S) (94,096 texters, 52.4%). During the pandemic, an increase in suicidal thoughts and active rescues occurred in the D/I/S and S/D higher-risk subclasses. Characteristics of vulnerable groups in higher-risk classes since the pandemic included children, LGBTQ, American Indian, White, Black, Asian, female, and gender-nonconforming youth., Conclusions: Results identified a strong association with class membership in more severe risk classes during the pandemic and an increase in suicidal help-seeking, particularly among children and LGBTQ youth. Low-cost and targeted crisis text-based platforms for support-seeking in youth may be one potential safety net strategy to address the effects of the COVID-19 pandemic on mental health in youth., (Copyright © 2021 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Research suggests that language barriers in health care settings may adversely affect clinical outcomes and patient satisfaction. We describe the characteristics of adults with limited English proficiency (LEP) and diagnosed HIV in the United States. The Medical Monitoring Project is a complex sample survey of adults with diagnosed HIV in the United States that uses two-stage, probability-proportional-to-size sampling. We analyzed weighted interview and medical record data collected from June 2015-May 2018. The prevalence of LEP among adults with HIV was 10%. Higher percentages of adults with LEP, compared with adults with English proficiency (EP), were female, Hispanic/Latino, less educated and poor, only had Ryan White HIV/AIDS Program (RWHAP) health care coverage, attended RWHAP-funded facilities, were satisfied with their HIV medical care, were prescribed antiretroviral therapy (ART), were virally suppressed and received testing for sexually transmitted diseases. We found no statistical difference in ART adherence among adults with LEP and EP. Despite the association between LEP and the risk for health disparities, more persons with LEP were virally suppressed compared with persons with EP. One possible explanation is attendance at RWHAP-funded facilities by adults with LEP; however, future studies are needed to explore other possible explanations.

Limited research has been conducted on the mental health concerns of frontline and essential workers and their children during the COVID-19 pandemic in the United States (U.S.). This study examined the association between working on the frontlines in the U.S. during the COVID-19 pandemic (March to July 2020) and personal crisis text concerns (e.g., self-harm, suicidal thoughts, anxiety/stress, and substance abuse) for frontline essential workers and the children of frontline workers. We used a novel data set from a crisis texting service, Crisis Text Line (CTL), that is widely used throughout the U.S. Generalized Estimating Equations examined the individual association between eight specific crisis types (Depression, Stress/Anxiety, Self-Harm, Suicidal Thoughts, Substance Abuse, Isolation, Relationship Issues, and Abuse) and being in frontline work or being a child of a frontline worker during the early phase of the pandemic. Using CTL concerns as a proxy for the prevalence of mental health issues, we found that children of workers, specifically the youngest demographic (13 years and under), females, and non-conforming youth had a higher risk of specific crisis events during the COVID-19 pandemic. Additionally, Hispanic children of workers reported higher rates of stress/anxiety, whereas African American children of workers had higher rates of abuse and depression. Frontline workers had a higher risk of suicidal thoughts, and the risk of crisis events was generally highest for non-binary, transgender, and male users. Increases in CTL usage among frontline workers were noted across 7-28 days after spikes in local COVID-19 cases. The research to date has focused on the mental health of frontline essential workers, but our study highlights troubling trends in psychological stress among children of these workers. Supportive interventions and mental health resources are needed not only for frontline essential workers, but for their children too., (Copyright © 2021 Elsevier Inc. All rights reserved.)

National guidelines recommend annual sexually transmitted infection testing for sexually active people living with human immunodeficiency virus, including transgender women. Using data from the US Medical Monitoring Project during 2015-2019, in the previous 12 months, 63.3% of sexually active transgender women who were human immunodeficiency virus positive were tested for syphilis, 56.6% for chlamydia, and 54.4% for gonorrhea., (Published by Oxford University Press for the Infectious Diseases Society of America 2021.)

Abstract: Failure to maintain viral suppression may be attributed to suboptimal care engagement. Using data collected during 2015-2018, we describe nationally representative estimates of engagement in care among US adults with diagnosed HIV, overall and by viral suppression. Of those who felt they did not receive enough care, we described detailed information on barriers to care by viral suppression. We reported weighted percentages and evaluated differences between groups using Rao-Scott chi-square tests (p < .05). Persons who were not virally suppressed were less likely to be retained in care (57.3 vs. 90.8%). Common barriers to care included life circumstances that impeded receipt of care (50.0%), financial barriers (34.5%), and not feeling sick enough to take medicine (32.0%). Barriers to care varied by viral suppression status, and people who were not virally suppressed were more likely to report more than one barrier to care. These findings demonstrate that barriers can be multifaceted; addressing barriers to care by expanding comprehensive care models in HIV care settings could improve clinical outcomes among people with HIV., (Copyright © 2021 Association of Nurses in AIDS Care.)

This naturalistic study among patients with alcohol dependence examined whether routine blood biomarkers could help to identify patients with high risk for relapse after withdrawal treatment. In a longitudinal study with 6-month follow-up among 133 patients with alcohol dependence who received inpatient alcohol withdrawal treatment, we investigated the usefulness of routine blood biomarkers and clinical and sociodemographic factors for potential outcome prediction and risk stratification. Baseline routine blood biomarkers (gamma-glutamyl transferase [GGT], alanine aminotransferase [ALT/GPT], aspartate aminotransferase [AST/GOT], mean cell volume of erythrocytes [MCV]), and clinical and sociodemographic characteristics were recorded at admission. Standardized 6 months' follow-up assessed outcome variables continuous abstinence, days of continuous abstinence, daily alcohol consumption and current abstinence. The combined threshold criterion of an AST:ALT ratio > 1.00 and MCV > 90.0 fl helped to identify high-risk patients. They had lower abstinence rates (P = 0.001), higher rates of daily alcohol consumption (P < 0.001) and shorter periods of continuous abstinence (P = 0.027) compared with low-risk patients who did not meet the threshold criterion. Regression analysis confirmed our hypothesis that the combination criterion is an individual baseline variable that significantly predicted parts of the respective outcome variances. Routinely assessed indirect alcohol biomarkers help to identify patients with high risk for relapse after alcohol withdrawal treatment. Clinical decision algorithms to identify patients with high risk for relapse after alcohol withdrawal treatment could include classical blood biomarkers in addition to clinical and sociodemographic items.

Due to the coronavirus disease 2019 (COVID-19) pandemic, many universities and outreach programs have switched to online learning platforms, which inhibits students from completing formative hands-on experiments. To address this, we developed a series of at-home experiments for undergraduate engineering students and adapted one of these experiments for outreach purposes. This experiment was well received by middle school students in the Young Eisner Scholars (YES) Program and resulted in significant learning gains by pre/post-test assessment. Additionally, students showed enhanced attitudes toward science after completing their at-home experiments, as measured by pre/post-surveys. These results motivate the use of similar at-home experiments with virtual instruction to remotely teach engineering concepts to diverse, underserved communities during the COVID-19 pandemic and beyond.

Purpose: Few studies have examined grief and bereavement in the context of a pandemic, particularly among young people during the ongoing COVID-19 pandemic., Methods: The objective of this study is to examine spatiotemporal clustering of bereavement using data from Crisis Text Line, an SMS-based intervention with widespread usage among youth and adolescents in the United States from January 2017 to September 2020., Results: Results found significant spatial clustering of bereavement during the pandemic period in the late summer months compared with the onset of the pandemic., Conclusion: Our study provides the first evidence of elevated bereavement in adolescents using a technique for rapidly identifying clusters of bereavement risk among this vulnerable subgroup. Findings can be leveraged for targeted interventions and supportive counseling in geographic hotspots., (Copyright © 2021 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

HIV clinical outcomes have not been fully assessed by place of birth at the national level. We analyzed the Medical Monitoring Project data, an annual cross-sectional survey designed to produce nationally representative estimates on adults with diagnosed HIV in the United States, collected during 2015-2017 ( n  = 7617). We compared sociodemographic, behavioral, and clinical outcomes by place of birth using Rao-Scott chi-square tests ( P  < .05). Overall, 13.6% of adults with diagnosed HIV were non-US-born. During the past 12 months, a higher percentage of non-US-born than US-born adults, respectively, were prescribed ART (89.4% vs. 84.1%), retained in care (87.1% vs. 80.0%), virally suppressed at the last test (77.2% vs. 70.9%), and had sustained viral suppression (70.9% vs. 63.3%). A lower percentage of non-US-born adults reported binge drinking (13.0% vs. 16.1%), using non-injection drugs (15.3% vs. 31.7%), and suffering from depression (15.9% vs. 23.3%) or anxiety (10.0% vs. 20.2%). A significantly higher percentage of non-US-born adults had Ryan White HIV/AIDS Program (RWHAP) coverage (54.4% vs. 43.1%) and attended a RWHAP-funded health care facility (73.9% vs. 66.6%). Factors contributing to better HIV clinical outcomes among non-US-born persons may include access to RWHAP coverage, lower levels of substance use, and better mental health.

During 2018, estimated incidence of human immunodeficiency virus (HIV) infection among Hispanic and Latino (Hispanic/Latino) persons in the United States was four times that of non-Hispanic White persons (1). Hispanic/Latino men who have sex with men (MSM) accounted for 24% (138,023) of U.S. MSM living with diagnosed HIV infection at the end of 2018 (1). Antiretroviral therapy (ART) adherence is crucial for viral suppression, which improves health outcomes and prevents HIV transmission (2). Barriers to ART adherence among Hispanic/Latino MSM have been explored in limited contexts (3); however, nationally representative analyses are lacking. The Medical Monitoring Project reports nationally representative estimates of behavioral and clinical experiences of U.S. adults with diagnosed HIV infection. This analysis used Medical Monitoring Project data collected during 2015-2019 to examine ART adherence and reasons for missing ART doses among HIV-positive Hispanic/Latino MSM (1,673). On a three-item ART adherence scale with 100 being perfect adherence, 77.3% had a score of ≥85. Younger age, poverty, recent drug use, depression, and unmet needs for ancillary services were predictors of lower ART adherence. The most common reason for missing an ART dose was forgetting; 63.9% of persons who missed ≥1 dose reported more than one reason. Interventions that support ART adherence and access to ancillary services among Hispanic/Latino MSM might help improve clinical outcomes and reduce transmission., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Purpose: Complementary and alternative medicine (CAM) use is common amongst cancer patients. However, there is growing concern about its safety and efficacy. Online crowdfunding campaigns represent a unique avenue to understand the cancer patient's perspective for using CAM or declining conventional cancer therapy (CCT)., Methods: Five hundred GoFundMe campaigns from 2012 to 2019 detailing financial need for cancer treatment were randomly selected and reviewed for endorsement of CAM use, reasons for using CAM, and reasons for declining CCT. Descriptive statistics were used to compare patient and campaign characteristics between 250 CAM users and 250 non-CAM users., Results: Compared to non-CAM users, CAM users were more likely to be female (70% vs. 54%, p < 0.01), to report more stage IV cancer (54% vs. 12%, p < 0.01), and to have a history of delayed, missed, or misdiagnosis (10% vs. 4%, p < 0.01). Reasons for using CAM include endorsing curative/therapeutic effects 212 (85%), pain/stress reduction 137 (55%), and dissatisfaction with current or past medical treatment options 105 (42%). 87 (35%) CAM users that declined CCT reported that they wanted to try to fight off cancer using CAM first 57 (61%), that CCT was too "toxic" to the body 39 (42%), and cancer was already too advanced, so that CCT would be futile or too aggressive 25 (27%)., Conclusion: Cancer patients on GoFundMe using CAM highly value quality of life, comfort, and autonomy. Physicians should educate themselves on CAM to set realistic expectations and provide comprehensive counseling of the risks and benefits of CAM usage to patients who choose to use CAM to either augment or completely replace CCT.

Hepatitis C (HCV) and HIV have common modes of transmission but information about HCV transmission risk, prevention, and treatment among persons with coinfection is lacking. The Medical Monitoring Project produces nationally representative estimates describing adults with diagnosed HIV in the United States. Using medical record data recorded during 6/2013-5/2017, we identified persons with detectable HCV RNA documented during the past 24 months. Among persons with coinfection, we described HCV transmission risk factors and receipt of HCV prevention services during the past 12 months and prescription of HCV treatment during the past 24 months. Overall, 4.9% had documented active HCV coinfection, among whom 30.2% were men who have sex with men (MSM), 6.7% reported injection drug use, and 62.1% were prescribed HCV treatment. Among MSM, 45.5% reported condomless anal sex and 42.3% received free condoms. Among persons who used drugs, 30.8% received drug or alcohol counseling, and among persons who injected drugs, 79.2% received sterile syringes. Among persons with HIV/HCV coinfection, recent drug injection was uncommon and most received sterile syringes. However, 1 in 3 were MSM, of whom half reported recent HCV sexual transmission risk behaviors. More than one-third of those with coinfection were not prescribed curative HCV treatment.

The Reactome Knowledgebase (https://reactome.org) provides molecular details of signal transduction, transport, DNA replication, metabolism and other cellular processes as an ordered network of molecular transformations in a single consistent data model, an extended version of a classic metabolic map. Reactome functions both as an archive of biological processes and as a tool for discovering functional relationships in data such as gene expression profiles or somatic mutation catalogs from tumor cells. To extend our ability to annotate human disease processes, we have implemented a new drug class and have used it initially to annotate drugs relevant to cardiovascular disease. Our annotation model depends on external domain experts to identify new areas for annotation and to review new content. New web pages facilitate recruitment of community experts and allow those who have contributed to Reactome to identify their contributions and link them to their ORCID records. To improve visualization of our content, we have implemented a new tool to automatically lay out the components of individual reactions with multiple options for downloading the reaction diagrams and associated data, and a new display of our event hierarchy that will facilitate visual interpretation of pathway analysis results., (© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.)

National guidelines recommend that HIV providers systematically monitor retention in care to identify and re-engage persons suboptimally in care. We described (1) U.S.-based outpatient HIV care facilities that systematically monitor retention in care, and (2) characteristics of patients attending facilities that monitored retention in care. We used data collected during 6/2014-5/2015 from the Medical Monitoring Project, an annual, cross-sectional survey that produces nationally representative estimates of characteristics of HIV-positive persons in medical care. We described systematic monitoring of retention in care among facilities and patients attending facilities providing this service using weighted percentages and 95% confidence intervals, and used Rao-Scott chi-square tests ( p  < .05) to assess differences by selected characteristics. Overall, 67% of facilities systematically monitored retention in care, and 81% of patients attended these facilities. Federally qualified health centers, community-based organizations, health departments, non-private practices, and Ryan White HIV/AIDS Program (RWHAP)-funded facilities were more likely to systematically monitor retention in care. Persons living in poverty, and those who were homeless or incarcerated, or injected drugs were more likely to attend facilities with this service. Although systematic monitoring of retention in care is accessible for many patients, improvements at other, non-RWHAP-funded facilities may help in reaching national prevention goals.

Relocation from one's birthplace may affect human immunodeficiency virus (HIV) outcomes, but national estimates of HIV outcomes among Hispanics/Latinos by place of birth are limited. We analyzed Medical Monitoring Project data collected in 2015-2018 from 2564 HIV-positive Hispanic/Latino adults and compared clinical outcomes between mainland US-born (referent group), Puerto Rican (PR-born), and those born outside the United States (non-US-born). We reported weighted percentages of characteristics and used logistic regression with predicted marginal means to examine differences between groups ( p < 0.05). PR-born Hispanics/Latinos were more likely to be prescribed antiretroviral therapy (ART) (94%) and retained in care (94%) than mainland-US-born (79% and 77%, respectively) and non-US-born (91% and 87%, respectively) Hispanics/Latinos. PR-born Hispanics/Latinos were more likely to have sustained viral suppression (75%) than mainland-US-born Hispanics/Latinos (57%). Non-US-born Hispanics/Latinos were more likely to be prescribed ART (91% vs. 79%), retained in care (87% vs. 77%), and have sustained viral suppression (74% vs. 57%) than mainland-US-born Hispanics/Latinos. Greater Ryan White HIV/AIDS-funded facility usage among PR-born, better mental health among non-US-born, and less drug use among PR-born and non-US-born Hispanics/Latinos may have contributed to better HIV outcomes. Expanding programs with comprehensive HIV/AIDS services, including for mental health and substance use, may reduce HIV outcome disparities among Hispanics/Latinos.

The United States spends more per capita on prescription drugs than do other high-income countries (1). In 2017, patients paid 14% of this cost out of pocket (2). Prescription drug cost-saving strategies, including nonadherence to medications due to cost concerns, have been documented among U.S. adults (3) and can negatively affect morbidity and, in the case of persons with human immunodeficiency virus (HIV) infection, can increase transmission risk (4,5). However, population-based data on prescription drug cost-saving strategies among U.S. persons with HIV are lacking. CDC's Medical Monitoring Project* analyzed cross-sectional, nationally representative, surveillance data on behaviors, medical care, and clinical outcomes among adults with HIV infection. During 2016-2017, 14% of persons with HIV infection used a prescription drug cost-saving strategy for any prescribed medication, and 7% had cost saving-related nonadherence. Nonadherence due to prescription drug costs was associated with reporting an unmet need for medications from the Ryan White AIDS Drug Assistance Program (ADAP), not having Medicaid coverage, and having private insurance. Persons who were nonadherent because of cost concerns were more likely to have visited an emergency department, have been hospitalized, and not be virally suppressed. Reducing barriers to ADAP and Medicaid coverage, in addition to reducing medication costs for persons with private insurance, might help to decrease nonadherence due to cost concerns and, thus contribute to improved viral suppression rates and other health outcomes among persons with HIV infection., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Previous research indicates a high burden of depression among adults living with HIV and an association between depression and poor HIV clinical outcomes. National estimates of diagnosed depression, depression treatment status, and association with HIV clinical outcomes are lacking. We used 2009-2014 data from the Medical Monitoring Project to estimate diagnosed depression, antidepressant treatment status, and associations with sustained viral suppression (all viral loads in past year < 200 copies/mL). Data were obtained through interview and medical record abstraction and were weighted to account for unequal selection probabilities and non-response. Of adults receiving HIV medical care in the U.S. and prescribed ART, 27% (95% confidence interval [CI] 25-29%) had diagnosed depression during the surveillance period; the majority (65%) were prescribed antidepressants. The percentage with sustained viral suppression was highest among those without depression (72%, CI 71-73%) and lowest among those with untreated depression (66%, CI 64-69%). Compared to those without depression, those with a depression diagnosis were less likely to achieve sustained viral suppression (aPR 0.95, CI 0.93-0.97); this association held for persons with treated depression compared to no depression (aPR 0.96, CI 0.94-0.99) and untreated depression compared to no depression (aPR 0.92, CI 0.89-0.96). The burden of depression among adults living with HIV in care is high. While in our study depression was only minimally associated with a lower prevalence of sustained viral suppression, diagnosing and treating depression in persons living with HIV remains crucial in order to improve mental health and avoid other poor health outcomes.

There is considerable debate in the public arena and among the professional mental health community around the media's role in increasing suicide risk following exposure to suicide-themed media in youth. A recent example involves the concerning reaction to the release of Netflix's controversial hit teen-suicide drama 13 Reasons Why. This follow-up study examined the association between the release of 13 Reasons Why Season 2 ( 13RW2 ), which coincided with two celebrity suicides, and national trends in crisis-related text conversations. We implemented an interrupted time series design to examine changes in daily counts of crisis texts aggregated at the national level following two events: (1) the release of 13RW2 and (2) celebrity suicide deaths of Anthony Bourdain and Kate Spade. We also performed a sub-analysis of suicide-related crisis conversations following each event . Crisis conversation volume was 42% higher after the release of 13RW2 for 6 of the 18 days of the study period, while crisis text usage was 51% higher for 9 out of the 18 days after the publicized celebrity suicide deaths. Both the release of 13RW2 and the celebrity suicides in the summer of 2018 were followed by an abrupt, but transient rise in crisis help-seeking among adolescents. Media outlets should consider pairing suicide-themed content with crisis support services as a core best practice to reduce the risk of population-level adverse reactions to suicide portrayals or coverage., (© 2019 The Authors.)

Objective: To describe delivery of recommended HIV care and work satisfaction among infectious disease (ID) physicians, non-ID physicians, nurse practitioners (NPs), and physician assistants (PAs)., Data Sources: Medical Monitoring Project 2013-2014 HIV Provider Survey., Study Design: Population-based complex sample survey., Data Collection/analysis Methods: We surveyed 2208 HIV care providers at 505 US HIV care facilities and computed weighted percentages of provider characteristics, stratified by provider type. Rao-Scott chi-square tests and logistic regression used to compare characteristics of ID physicians with each other provider type., Principal Findings: The adjusted provider response rate was 64 percent. Among US HIV care providers, 45 percent were ID physicians, 35 percent non-ID physicians, 15 percent NPs, and 5 percent PAs. Satisfaction with administrative burden was lowest among non-ID physicians (27 percent). Compared with ID physicians, satisfaction with remuneration was lower among non-ID physicians and higher among NPs (37, 28, and 51 percent, respectively). NPs were more likely than ID physicians to report performing four of six services that are key to providing comprehensive HIV care, but more NPs planned to leave clinical practice within 5 years (19 vs 7 percent)., Conclusion: Addressing physician dissatisfaction with remuneration and administrative burden could help prevent a provider shortage. Strengthening the role of NPs may help sustain a high-quality workforce., (© Health Research and Educational Trust.)

Purpose: Endoscopic dextranomer/hyaluronic acid (Dx/HA) injection is a common treatment for vesicoureteral reflux (VUR) with excellent reported short-term clinical success rates. Long-term outcomes are less well-defined. We assessed long-term outcomes and parental satisfaction after Dx/HA injection for primary VUR with >5-year follow-up. Materials and Methods: Families of all patients who underwent Dx/HA injection for primary VUR at our institution between 2008 and 2012 were contacted for telephone interview. Data collected by phone included parental satisfaction and presence and severity of UTIs pre-operatively and post-operatively. Patient demographics, radiographic VUR data, need for secondary surgery, and surgical indications were obtained through chart review. Results: Five hundred and seventy-five patients underwent Dx/HA injection for primary VUR between 2008 and 2012. Ninety-nine (17.2%) of these patients' parents were successfully contacted and interviewed. Median follow-up time from surgery to survey was 8.4 (IQR 6.8-9.6) years. Secondary surgery was performed in 13/99 (13.1%), most commonly repeat Dx/HA injection. Seven patients (7.1%) underwent secondary Dx/HA injection for persistent VUR without UTIs at a median of 0.35 (IQR 0.33-0.77) years post-operatively. Five patients (5.1%) underwent Dx/HA injection ( n = 3) or ureteral reimplantation ( n = 2) for VUR with febrile UTIs (fUTIs) at a median of 2.2 (IQR 1.3-5.1) years. One patient had ureteral reimplantation for symptomatic obstruction 2.8 years after initial surgery. Only 3/99 (3.0%) required open or laparoscopic surgery after Dx/HA injection. Eighty-three families (84.7%) reported ≥1 fUTIs pre-operatively. Of these, only 9/83 (10.8%) reported fUTIs post-operatively, for an overall clinical success rate of 89.2%. Clinical success was 93.1% in patients whose pre-operative fUTIs were treated outpatient and 80.0% in those hospitalized at least once for fUTI treatment pre-operatively. Ninety-four percent of parents were highly satisfied, 2.4% partially satisfied, and 3.5% dissatisfied. Conclusions: Endoscopic injection with Dx/HA for primary VUR appears to have good long-term clinical success rates and high parental satisfaction, mirroring our previously reported short-term results. Post-operative ureteral obstruction is rare but may occur years post-operatively, justifying initial sonographic surveillance, and repeat imaging in symptomatic patients., (Copyright © 2019 Lightfoot, Bilgutay, Tollin, Eisenberg, Weiser, Bryan, Smith, Elmore, Scherz and Kirsch.)